Substituted n-aryl benzamides and related compounds for treatment of amyloid diseases and synucleinopathies

Abstract

Compounds and their pharmaceutically acceptable salts, their synthesis and labeling, pharmaceutical compositions containing them, and their use in the treatment of amyloid diseases, including Aβ amyloidosis, such as observed in Alzheimer's disease, IAPP amyloidosis, such as observed in type 2 diabetes, and synucleinopathies, such as observed in Parkinson's disease, and the manufacture of medicaments for such treatment are provided. Also provided is the use of the disclosed compounds as imaging agents and methods for in vivo imaging and detection of amyloid and synuclein.

Description

RELATED APPLICATIONS[0001]This application is a continuation in part of U.S. application Ser. No. 12 / 201,183 filed Aug. 29, 2008 which is a continuation in part of U.S. application Ser. No. 11 / 328,748, now issued U.S. Pat. No. 7,745,490, which is a continuation of U.S. application Ser. No. 11 / 129,771, filed May 12, 2005, entitled “Substituted N-Aryl Benzamides and Related Compounds for Treatment of Amyloid Diseases and Synucleinopathies” now abandoned. U.S. application Ser. No. 11 / 129,771 claimed priority under 35 U.S.C. §119(e) to U.S. provisional application Ser. Nos. 60 / 570,669, entitled “Substituted N-Aryl Benzamides and Related Compounds for Treatment of Amyloid Diseases and Synucleinopathies” to Snow et al., filed May 12, 2004 and 60 / 629,525, entitled “Substituted N-Aryl Benzamides and Related Compounds for Treatment of Amyloid Diseases and Synucleinopathies” to Snow et al., filed Nov. 18, 2004.[0002]This application is also a continuation in part of U.S. application Ser. No. ...

AI Technical Summary

Benefits of technology

The patent text describes compounds and pharmaceutical compositions containing these compounds that can be used to treat amyloid diseases and synucleinopathies. These compounds have been designed to optimize their physicochemical and biological properties, such as bioavailability and pharmacokinetics, to enhance their efficacy in treating these diseases. The compounds can be administered through various routes, such as injection, oral, or nasal, and can be formulated as solutions, suspensions, emulsions, tablets, or powders. The methods described in the patent text can be used to disrupt, disaggregate, or remove amyloid or synuclein fibrils, providing new treatments for these diseases.

Problems solved by technology

Fibrillar Aβ amyloid deposition in Alzheimer's disease is believed to be detrimental to the patient and eventually leads to toxicity and neuronal cell death, characteristic hallmarks of Alzheimer's disease.

In Alzheimer's disease, Parkinson's and “systemic” amyloid diseases, there is currently no cure or effective treatment, and the patient usually dies within 3 to 10 years from disease onset.

For most of these amyloidoses, there is no apparent cure or effective treatment and the consequences of amyloid deposition can be detrimental to the patient.

For example, amyloid deposition in the kidney may lead to renal failure, whereas amyloid deposition in the heart may lead to heart failure.

Alzheimer's disease also puts a heavy economic burden on society.

For a disease that can span from 2 to 20 years, the overall cost of Alzheimer's disease to families and to society is staggering.

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